Vectors with modified protease-dependent tropism

A complex comprising a genomic RNA of paramyxovirus wherein the genomic RNA comprises:

• (a) a nucleic acid encoding an M protein that is mutated or deleted, and (b) a nucleic acid encoding a modified F protein whose cleavage site sequence is substituted with a sequence that can be cleaved by a protease that does not cleave the wild-type F protein, and wherein the modified F protein is fused with an HN protein, said complex further comprising the following properties:
• (1) the ability to replicate the genomic RNA in a cell to which the complex has been introduced;
• (2) a significant decrease in or lack of production of viral particles in an intrahost environment;
• and
• (3) the ability to introduce the RNA into a cell that contacts with a cell transfected with the complex in the presence of the protease.

A method for producing a viral particle which comprises a genomic RNA of paramyxovirus wherein the genomic RNA comprises:

• (a) a nucleic acid encoding an M protein that is mutated or deleted, and (b) a nucleic acid encoding a modified F protein, whose cleavage site sequence is substituted with a sequence that can be cleaved by a protease that does not cleave the wild-type F protein;
• wherein the viral particle:
• (1) has the ability to replicate the genomic RNA in a cell to which the viral particle has been introduced;
• (2) shows a significant decrease in or lack of production of viral particles in an intrahost environment;
• and
• (3) has the ability to introduce the genomic RNA into a cell that contacts with a cell infected with the viral particle comprising the genomic RNA in the presence of the protease;
• said method comprising the steps of:
• (i) amplifying a viral particle, which comprises the N, P, and L proteins of the paramyxovirus and the genomic RNA, in a cell expressing wild-type M protein and wild-type F protein of paramyxovirus;
• and
• (ii) collecting viral particles released into the cell culture supernatant;
• wherein the viral particles are activated by presenting the protease that cleaves the wild-type F protein during at least either of step (i) or (ii), or by the step of treating the viral particle collected in the step (ii) with the protease.